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L Stinus

Publications and source records attributed to L Stinus.

At least 91 records · Page 5Linked to original sources

[Effects of lesions of the anterior raphe nuclei on the self-administration of d-amphetamine in the rat : considerable increase of desire for the poison].

The acquisition of the intravenous self-administration of d-amphetamine was studied after separate lesions of anterior raphe nuclei (dorsal or median). Every lever-press delivered 2.5 microliter of a d-amphetamine solution dosed at 7.5 microgram/kg. Lesion of anterior raphe nuclei produced an hyper-sensitivity to d-amphetamine as indicated by a dramatic increase in self-administration by experimental Rats compared to the controls. Moreover this enhanced self-administration behavior is observed with a low blood concentration of d-amphetamine. The greater increase was obtained for median raphe lesioned Rats. These effects are interpreted in terms of 5HT-DA balance and could provide an experimental model for neurobiological bases of drug addiction studies.

Animals↗

Locomotor hyperactivity and hypoexploration after lesion of the dopaminergic-A10 area in the ventral mesencephalic tegmentum (VMT) of rats.

The lesion of the ventral mesencephalic tegmentum (VMT) and especially of the dopaminergic (DA) A10 neurons induced disturbances of spontaneous activity in the rat. Measured in different situations (circular corridor, open field, hole box), locomotor activity was dramatically and permanently increased (5 days of recording) without modifications of the circadian rhythm, although exploratory patterns of behavior were reduced. In contrast, the administration of a low dose of D-amphetamine (1 and 2 mg/kg i.p.) to naïve rats induced an increase of both locomotor and exploratory activities. A qualitative analysis of spontaneous activity of rats after VMT lesions and after administration of D-amph, revealed opposing aspects of behavior. Residual response to D-amph of VMT-lesioned rats suggest a subtotal destruction of DA-A10 neurons, the implication of an over activity of these remaining DA-A10 neurons on behavioral deficit is considered. Our results can be explained by a deficiency in attention processes.

Animals↗

Interactions between D-ala-met-enkephalin, A10 dopaminergic neurones, and spontaneous behaviour in the rat.

We have investigated the interaction between opioid peptides and dopaminergic A10 (DA-A10) neurones in the ventral tegmental area (VTA). The behavioural consequences of VTA infusion of d-Ala-Met-enkephalinamide (DALA) were analyzed. DALA elicited a dose-dependent increase in locomotor activity measured in photocell cages and the circular corridor. Observations in the open field and in a hole box revealed that DALA-induced behavioural stimulation was characterized by enhancement of locomotion, rearing, and number of hole visits, while grooming time and duration of hole visits were decreased. DALA-induced stimulation was reserved by naloxone, and was completely blocked by 6-OHDA destruction of DA-A10 terminals. d-Amphetamine-induced behavioural activation was potentiated by simultaneous VTA infusion of DALA which indicates that the behavioural response to DALA is dependent on DA-A10 neuronal activity. It is postulated that stimulation of opiate receptors exerts a presynaptic inhibition of an inhibitory input to DA-A10 neurones (eg. GABA or dendritic DA), thus releasing dopaminergic activity. In contrast to the acute effect, the d-amphetamine response was strongly attenuated 4 h, 1 and 6 days after VTA infusion of DALA, and returned to normal only at 14 days. This long-lasting modification may reflect decreased activity of opioid neurones, releasing the inhibition of DA-A10 neurones. Our findings suggest that endogenous opioid peptides may exert a modulatory influence on the dopaminergic mesocorticolimbic system.

Animals↗

Locomotor activation induced by infusion of endorphins into the ventral tegmental area: evidence for opiate-dopamine interactions.

beta-Endorphin in nanomole quantities produced a stimulation of locomotor activity when infused into the region of the dopamine cell bodies of the ventral tegmental area (VTA) in rats. alpha-, gamma-, and des-Tyr-gamma-endorphin produced similar effects, but the D-alanine analogues of alpha and gamma-endorphin produced a larger and longer-lasting activation, presumably reflecting their resistance to degradation. This locomotor activation was reversible by pretreatment with naloxone and by destruction of the terminal projections of the mesocorticolimbic dopamine system originating in the VTA. These results demonstrate that locally infused endorphin can interact with the opioid receptors in the VTA, and they suggest a means by which endorphins activate limbic excitability.

Animals↗

Anatomical relationships between the ventral mesencephalic tegmentum--a 10 region and the locus coeruleus as demonstrated by anterograde and retrograde tracing techniques.

We have searched for anatomical connections between the ventral mesencephalic tegmentum (VMT), including the dopaminergic cell group A10 and the locus coeruleus (LC) region. Tritiated leucine (120--220 nl) and horseradish peroxidase delivered by electrophoresis were injected in the VMT-A10 region. We have demonstrated, on the one hand bilateral projections from the VMT-A10 region to LC, and on the other hand a possible contralateral projection from LC to VMT-A10 region. These relationships, reported for the first time may have some important functional significance.

Animals↗

Behavioural activation induced in the rat by substance P infusion into ventral tegmental area: implication of dopaminergic A10 neurones.

The functional role of the putative transmitter substance P (SP) was studied using a behavioural approach. SP infusion into the ventral tegmental area in awake rats elicited an increase in locomotor activity which could be blocked by either infusion of a neuroleptic into the nucleus accumbens septi (NAS) or by 6-hydroxydopamine (6-OHDA) lesions of the ascending dopaminergic A10 neurones. Our results suggest that SP induces its behavioural effects through activation of dopaminergic A10 neurones, and imply that endogenous SP may have an important modulatory role.

Animals↗

Topographical distribution of dopaminergic innervation and dopaminergic receptors of the anterior cerebral cortex of the rat.

The quantitative topographical distribution of the dopaminergic innervation and the DA-sensitive adenylate cyclase were estimated in the anterior cerebral cortex of the rat. The high affinity uptake of [3H]DA and endogenous levels of DA were used as markers of the dopaminergic innervation. [3H]DA uptake, DA levels and DA-sensitive adenylate cyclase were estimated in microdiscs of tissues punched out from frozen serial frontal slices. The uptake of [3H]DA was measured on sucrose homogenates prepared from such microdiscs. The ventral part of the frontal cortex contained the highest DA concentration and DA-sensitive adenylate cyclase activity; the other structures rich in DA and in DA receptors were the cingular (close to the corpus callsoum) and the rhinal cortices. All of these cortical areas were rich in [3H]DA uptake sites. However, curiously, the dorsal part of the frontal cortex, which contained only moderate amounts of DA and of DA-sensitive adenylate cyclase, presented the highest number of [3H]DA uptake sites. Nevertheless, the uptake of [3H]DA in this region decreased by 60% after bilateral electrolytical lesions of the ventral tegmental area (A10 group). The parietal cortex was practically devoid of dopaminergic innervation and of DA-sensitive adenylate cyclase. The activity of the DA-sensitive adenylate cyclase in the frontal, cingular and rhinal cortices was 10-fold higher than that found in the striatum when compared to their respective DA levels.

Adenylyl Cyclases↗

Disappearance of hoarding and disorganization of eating behavior after ventral mesencephalic tegmentum lesions in rats.

The effects of ventral mesencephalic tegmentum (VMT) radio-frequency lessions on spontaneous and complex behaviors, such as food hoarding and alimentary patterns, were investigated. Activity measures indicated that VMT lesions increased horizontal activity in a circular corridor as well as in an open field whereas vertical activity (rearing) was decreased. After 12 hr of food deprivation, food hoarding and alimentary patterns were evaluated in a square open field to which rats had free access from their home cage. Control rats hoarded food and had organized feeding behavior, but experimental rats did not hoard. Moreover, increasing the open-field illumination did not reverse this deficit. Similarly, the VMT lesion induced disruption of the adaptative alimentary behavior in response to food deprivation. A strong correlation was observed between hoarding scores and the extent of locomotor hyperactivity. These results are discussed in terms of a possible implication of limbic-midbrain mechanisms in which the meso-cortico-limbic dopaminergic A10 neurons originating in the VMT might have a primary role.

Animals↗

Small doses of apomorphine and chronic administration of d-amphetamine reduce locomotor hyperactivity produced by radiofrequency lesions of dopaminergic A10 neurons area.

The lesion of the ventral mesencephalic tegmentum region (VMT) induces a behavioral syndrome characterized mainly by locomotor hyperactivity and reduction of attention processes. Previous data indicated that this syndrome was due at least in part to the destruction of dopaminergic (DA) A10 neurons. In order to test this hypothesis, we examined the effects of two dopaminomimetics drugs: apomorphine (APO) and d-amphetamine (d-AMPH) on the VMT behavioral syndrome. The acute administration of very low doses of APO (30 microgram/KG; Sc) reduces the behavioral deficits; similarly a chronic administration of d-aMPH (two injections daily for 43 days) reduces locomotor hyperactivity. In these two cases, the lesioned rats activity reaches the control level. These results confirm the primary role of DA-A10 neurons in the VMT behavioral syndrome. Acute APO and chronic d-AMPH effects are discussed in terms of (i) reactivation of DA postsynaptic receptors disafferented after DA-A10 group destruction and (ii) strengthening of the hyperfunctioning of the remaining DA-A10 neurons. VMT-A10 syndrome could be a good animal model for pathophysiological studies.

Animals↗

Effects of various inhibitors of tyrosine hydroxylase and dopamine beta-hydroxylase on rat self-stimulation after reserpine treatment.

The behavioral effects of low doses of the catecholamine (CA) synthesis inhibitor, alpha-methyl-p-tyrosine (alpha-MPT, 50 mg/kg i.p.), or the norepinephrine (NE) synthesis inhibitors (FLA-63, 15 mg/kg i.p., U-14624, 50 mg/kg i.p., or disulfiram 150 mg/kg i.p.) were studied in rats pretreated with reserpine (1 mg/kg i.p.) 24 h before. Rats were implanted either in the area ventralis tegmenti (AVT) or in the lateral hypothalamus (LH). The modifications of CA synthesis and endogenous CA levels were estimated in a parallel experiment. Reserpine treatment produced a slow decrease in self-stimulation (SS) rates during the first 12 h; SS rates were 85% of control values 24 h after reserpine treatment. Injection of alpha-MPT in reserpine-pretreated rats inhibited SS (85% decrease 3 h after administration either in AVT or LH rats), whereas dopamine beta-hydroxylase inhibition had no great effect on SS. The administration of very low doses of alpha-MPT (20 mg/kg i.p.) to rats treated with reserpine (24 h before) plus FLA-63 (1 h before) induced an important decrease in SS rates in AVT-implanted rats only. The major conclusion is that dopaminergic neurons seem to be involved in AVT and LH SS. The last experiment suggests the involvement of a balance between dopaminergic and noradrenergic neurons in AVT SS.

Animals↗